Exosomes from hepatitis B virus‐infected hepatocytes activate hepatic stellate cells and aggravate liver fibrosis through the miR‐506‐3p/Nur77 pathway

Abstract Cumulative evidence indicates the important role of Nur77 in organ fibrogenesis. However, the role of Nur77 in hepatitis B virus (HBV)‐related liver fibrosis (LF) remains unclear. Cells were transfected with the microRNA mimic miRNA‐506‐3p or inhibitor, and pcDNA3.1‐Nur77 or Nur77 guide RNA. Exosomes were isolated from HBV‐infected HepG2‐sodium taurocholate cotransporting polypeptide cells. The levels of miR‐506‐3p, Nur77, and LF‐related genes and proteins were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The pathology of the liver from HBV‐infected patients was examined using hematoxylin‐eosin and Masson's staining. The expression of Nur77 in liver tissue was determined by immunohistochemistry, and the LF score was assessed using the METAVIR system. The relationship between miR‐506‐3p/Nur77 and LF score was analyzed by correlation analysis. HBV infection downregulated miR‐506‐3p expression and upregulated Nur77 levels in hepatocytes. Exosomes from HBV‐infected hepatocytes also displayed decreased gene expression of miR‐506‐3p and increased expressions of Nur77‐ and LF‐related genes in stellate cells compared with exosomes from hepatocytes with mock infection. These changes were reversed by Nur77 guide RNA. Nur77 expression in liver tissue was strongly correlated with LF, whereas serum miR‐506‐3p was strongly negatively correlated with LF. Exosomes from HBV‐infected hepatocytes activate stellate cells and aggravate LF through the miR‐506‐3p/Nur77 pathway. These exosomes may be the basis of a promising therapeutic strategy.